Optimal single sampling time-point for monitoring of praziquantel exposure in children
Abstract Praziquantel pharmacokinetics studies in schistosomiasis infected children are scarce partly due to the challenges/complexity of intensive blood sampling in the target population. This study was aimed to investigate the optimal single sampling time-point for monitoring praziquantel exposure...
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| Format: | Article |
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Nature Portfolio
2021-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-97409-x |
| _version_ | 1818993541554110464 |
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| author | Rajabu Hussein Mnkugwe Eliford Ngaimisi Kitabi Safari Kinung’hi Appolinary A. R. Kamuhabwa Omary Mashiku Minzi Eleni Aklillu |
| author_facet | Rajabu Hussein Mnkugwe Eliford Ngaimisi Kitabi Safari Kinung’hi Appolinary A. R. Kamuhabwa Omary Mashiku Minzi Eleni Aklillu |
| author_sort | Rajabu Hussein Mnkugwe |
| collection | DOAJ |
| description | Abstract Praziquantel pharmacokinetics studies in schistosomiasis infected children are scarce partly due to the challenges/complexity of intensive blood sampling in the target population. This study was aimed to investigate the optimal single sampling time-point for monitoring praziquantel exposure. This was intensive pharmacokinetic study conducted among 32 Schistosoma mansoni infected children treated with an oral standard single-dose 40 mg/kg praziquantel. Plasma samples were collected at 0, 1, 2, 4, 6 and 8 h post-praziquantel administration. Quantification of praziquantel and its enantiomers (R- and S-praziquantel) concentrations was done by Liquid chromatography-tandem mass spectrometer (LC–MS/MS). The correlation between area under the plasma concentration–time curve from 0 to 8 h (AUC8) and plasma concentrations at each specific sampling time-point was determined by Pearson’s correlation coefficient (r2). The median age (range) of the study population was 12.5 years (10–17). The study participants were 17 males and 15 females. Both total praziquantel and its enantiomers (R- and S-praziquantel) displayed a wide inter-individual pharmacokinetic variability. Regression analysis indicated that, plasma concentrations collected at 4 h post-dose had a significantly highest correlation with the AUC8 for both total praziquantel (r2 = 0.81, p < 0.001) and S-praziquantel (r2 = 0.84, p < 0.001) than any other sampling time-point; while for R-praziquantel, plasma concentrations collected at 6 h sampling time-point had a significantly highest correlation with the AUC8 (r2 = 0.79, p < 0.001) than any other sampling time-point. Four hours sampling time-point post-praziquantel administration is ideal optimal single sampling time-point for therapeutic monitoring of total praziquantel exposure while 6 h sampling time-point is suitable for monitoring of a pharmacologically active R-praziquantel enantiomer. |
| first_indexed | 2024-12-20T20:43:42Z |
| format | Article |
| id | doaj.art-94f4d46daa4948c4ba9c381e4f310157 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T20:43:42Z |
| publishDate | 2021-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-94f4d46daa4948c4ba9c381e4f3101572022-12-21T19:27:06ZengNature PortfolioScientific Reports2045-23222021-09-011111910.1038/s41598-021-97409-xOptimal single sampling time-point for monitoring of praziquantel exposure in childrenRajabu Hussein Mnkugwe0Eliford Ngaimisi Kitabi1Safari Kinung’hi2Appolinary A. R. Kamuhabwa3Omary Mashiku Minzi4Eleni Aklillu5Department of Clinical Pharmacology, School of Medicine, Muhimbili University of Health and Allied SciencesOffice of Clinical Pharmacology, Division of Pharmacometrics, Food and Drugs AdministrationNational Institute for Medical Research, Mwanza Research CentreDepartment of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied SciencesDepartment of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied SciencesDivision of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska InstitutetAbstract Praziquantel pharmacokinetics studies in schistosomiasis infected children are scarce partly due to the challenges/complexity of intensive blood sampling in the target population. This study was aimed to investigate the optimal single sampling time-point for monitoring praziquantel exposure. This was intensive pharmacokinetic study conducted among 32 Schistosoma mansoni infected children treated with an oral standard single-dose 40 mg/kg praziquantel. Plasma samples were collected at 0, 1, 2, 4, 6 and 8 h post-praziquantel administration. Quantification of praziquantel and its enantiomers (R- and S-praziquantel) concentrations was done by Liquid chromatography-tandem mass spectrometer (LC–MS/MS). The correlation between area under the plasma concentration–time curve from 0 to 8 h (AUC8) and plasma concentrations at each specific sampling time-point was determined by Pearson’s correlation coefficient (r2). The median age (range) of the study population was 12.5 years (10–17). The study participants were 17 males and 15 females. Both total praziquantel and its enantiomers (R- and S-praziquantel) displayed a wide inter-individual pharmacokinetic variability. Regression analysis indicated that, plasma concentrations collected at 4 h post-dose had a significantly highest correlation with the AUC8 for both total praziquantel (r2 = 0.81, p < 0.001) and S-praziquantel (r2 = 0.84, p < 0.001) than any other sampling time-point; while for R-praziquantel, plasma concentrations collected at 6 h sampling time-point had a significantly highest correlation with the AUC8 (r2 = 0.79, p < 0.001) than any other sampling time-point. Four hours sampling time-point post-praziquantel administration is ideal optimal single sampling time-point for therapeutic monitoring of total praziquantel exposure while 6 h sampling time-point is suitable for monitoring of a pharmacologically active R-praziquantel enantiomer.https://doi.org/10.1038/s41598-021-97409-x |
| spellingShingle | Rajabu Hussein Mnkugwe Eliford Ngaimisi Kitabi Safari Kinung’hi Appolinary A. R. Kamuhabwa Omary Mashiku Minzi Eleni Aklillu Optimal single sampling time-point for monitoring of praziquantel exposure in children Scientific Reports |
| title | Optimal single sampling time-point for monitoring of praziquantel exposure in children |
| title_full | Optimal single sampling time-point for monitoring of praziquantel exposure in children |
| title_fullStr | Optimal single sampling time-point for monitoring of praziquantel exposure in children |
| title_full_unstemmed | Optimal single sampling time-point for monitoring of praziquantel exposure in children |
| title_short | Optimal single sampling time-point for monitoring of praziquantel exposure in children |
| title_sort | optimal single sampling time point for monitoring of praziquantel exposure in children |
| url | https://doi.org/10.1038/s41598-021-97409-x |
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